Water → 3-[3-(7-Methylimidazo[1,2-alpha]pyridin-3-yl)phenyl]thiophene-2-carbonitrile

HRID 985505Notes

Reaction equation

HRID 985505 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](B4OC(C)(C)C(C)(C)O4)[CH:12]=3)=[CH:9][N:10]=[C:4]2[CH:3]=1.Br[C:27]1[CH:31]=[CH:30][S:29][C:28]=1[C:32]#[N:33].O>COCCOC.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:12]=[C:13]([C:27]4[CH:31]=[CH:30][S:29][C:28]=4[C:32]#[N:33])[CH:14]=[CH:15][CH:16]=3)=[CH:9][N:10]=[C:4]2[CH:3]=1

Participants

7

Reactant 3

HCID 962WaterHCID 27400883-Bromothiophene-2-carbonitrileHCID 114937107-Methyl-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]imidazo[1,2-alpha]pyridine

Product 1

HCID 97969523-[3-(7-Methylimidazo[1,2-alpha]pyridin-3-yl)phenyl]thiophene-2-carbonitrileYield 57.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10796Cesium carbonateSolvent

Procedure

A mixture of 7-methyl-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]imidazo[1,2-α]pyridine (350 mg, 1.0 mmol) and 3-bromo-2-cyanothiophene (200 mg, 1.0 mmol) in 1,2-dimethoxyethane (10 ml) and caesium carbonate (5 ml of a 2M solution) was degassed for 15 minutes. Tetrakis(triphenylphosphine)palladium(0) (125 mg, 0.1 mmol) was then added and the mixture heated at reflux for 20 hours, poured into water (50 ml) and extracted with ethyl acetate (2×25 ml). The combined organic phases were dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo. Purification by flash chromatography eluting with 3% methanol in dichloromethane gave the title compound as a colourless oil (180 mg, 57%). Oxalate salt, white powder, m.p. 193-195° C. (Found C, 62.07; H, 3.66; N, 10.19. C19H13N3S.C2H2O4 requires C, 62.21; H, 3.73; N, 10.36). 1H NMR (360 MHz, d6-DMSO) δH 2.42 (3H, s), 6.91-6.93 (1H, m), 7.53 (1H, s), 7.68-7.82 (6H, m), 7.89 (1H, s), 8.01 (1H, s), 8.18 (1H, d, J 5), 8.63 (1H, d, J 7); m/z (ES+) 316 (M++H).

Workup

  1. customwas degassed for 15 minutes
  2. temperaturethe mixture heated
  3. temperatureat reflux for 20 hours
  4. extractionextracted with ethyl acetate (2×25 ml)
  5. dry with materialThe combined organic phases were dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography
  9. washeluting with 3% methanol in dichloromethane

Sources & evidence

ORD record
ord-984c98e84c9440f8bed531b864184915
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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